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Trial record 1 of 2 for:    smm2001
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A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02316106
Recruitment Status : Active, not recruiting
First Posted : December 12, 2014
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE December 10, 2014
First Posted Date  ICMJE December 12, 2014
Last Update Posted Date May 20, 2020
Actual Study Start Date  ICMJE May 20, 2015
Estimated Primary Completion Date August 6, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • The percentage of participants who achieve a complete response (CR) [ Time Frame: Up to approximately 5 years ]
    CR, defined having negative immunofixation on the serum and urine, and <5% plasma cells (PCs) in bone marrow.
  • The percentage of participants that have an event (disease progression or death) per patient-year [ Time Frame: Up to approximately 5.5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2014)
  • The percentage of participants who achieve a complete response (CR) [ Time Frame: Up to approximately 24 months ]
    CR, defined having negative immunofixation on the serum and urine, and <5% plasma cells (PCs) in bone marrow.
  • The percentage of participants that have an event (disease progression or death) per patient-year [ Time Frame: Up to approximately 30 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
  • The percentage of participants who are minimal residual disease (MRD) negative [ Time Frame: Up to 5.5 years ]
  • Time to next treatment (TNT) [ Time Frame: Up to 5.5 years ]
    TNT, defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment.
  • The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR) [ Time Frame: Up to 5.5 years ]
    See definition of CR above. PR, defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.
  • The median time of progression free survival (PFS) [ Time Frame: Up to 5.5 years ]
    PFS is defined as time from date of randomization to date of initial documented disease progression (PD) according to SLiM-CRAB (S=sixty, Li=light chains, M=MRI, C=calcium [elevated], R=renal failure, A=anemia, B=bone lesions) criteria, myeloma defining events, or date of death, whichever occurs first. As per SLiM-CRAB criteria, clonal bone marrow plasma cell percentage >=60%, Involved : uninvolved serum free Li ratio >= 100, >1 focal lesion on MRI studies, calcium elevation: >0.25 millimole per liter (mmol/L) ( >1 milligram per deciliter [mg/dL]) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL); creatinine clearance <40 milliliter per minute (mL/min) or serum creatinine >177 micromole per liter (µmol/L) (>2 mg/dL); hemoglobin <10 gram per deciliter (g/dL) (<6.5 mmol/L) or >2 g/dL (>1.25 mmol/L) lower than lower limit of normal; 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT).
  • The percentage of participants with symptomatic multiple myeloma [ Time Frame: Up to 5.5 years ]
  • Response to first subsequent multiple myeloma treatment [ Time Frame: Up to 5.5 years ]
  • Overall survival rate [ Time Frame: Up to 5.5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2014)
  • The percentage of participants who are minimal residual disease (MRD) negative [ Time Frame: Up to 5.5 years ]
  • Time to next treatment (TNT) [ Time Frame: Up to 5.5 years ]
    TNT, defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment.
  • The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR) [ Time Frame: Up to 5.5 years ]
    See definition of CR above. PR, defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours.
  • The median time of progression free survival (PFS) [ Time Frame: Up to 5.5 years ]
    PFS, defined as the time from the date of randomization to the date of initial documented disease progression (PD) or date of death, whichever occurs first.
  • The percentage of participants with symptomatic multiple myeloma [ Time Frame: Up to 5.5 years ]
  • Response to first subsequent multiple myeloma treatment [ Time Frame: Up to 5.5 years ]
  • Overall survival rate [ Time Frame: Up to 5.5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma
Official Title  ICMJE A Randomized Phase 2 Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Multiple Myeloma
Brief Summary The purpose of this study is to evaluate three daratumumab dose schedules in participants with Smoldering Multiple Myeloma.
Detailed Description This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab in participants diagnosed with intermediate or high-risk Smoldering Multiple Myeloma (SMM [ie, early disease without any symptoms]). Participants will be randomized (assigned by chance) to one of 3 treatment groups (arm A [long intense], arm B [intermediate] and arm C [short intense]) to receive daratumumab. Each treatment group will investigate 1 of 3 dosing schedules of daratumumab. The study will include a 28-Day Screening Phase, a Treatment Phase of 1 to 20 treatment cycles (each cycle is 8 weeks in duration for total period of 8 to 160 weeks), and a Follow up Phase of 4-weeks from the last dose of study drug. For participants in Arm A (long intense) and Arm B (intermediate), there is a possibility to extend treatment with IV daratumumab (Q8W) after the end of Cycle 20 if, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade >=3 treatment related toxicity, and at least stable disease has been achieved. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w). The Follow-up Phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. The end of the study will occur approximately 5 years after the last participant enrolled receives a first dose of study drug. 'Disease assessment will be performed locally per Standard of Care.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: daratumumab
    16 mg/kg administered by intravenous (IV) infusion once every week in Cycle 1, every other week in Cycle 2 and Cycle 3, every 4 weeks in Cycle 4 to Cycle 7, and from Cycle 8 to Cycle 20 on Day 1 of each cycle. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w).
  • Drug: daratumumab
    16 mg/kg administered by IV infusion once every week in Cycle 1, and then on Day 1 of each cycle from Cycle 2 to Cycle 20, and every 8 weeks after Cycle 20. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w).
  • Drug: daratumumab
    16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.
Study Arms  ICMJE
  • Experimental: Arm A (Long Intense)
    Intervention: Drug: daratumumab
  • Experimental: Arm B (Intermediate)
    Intervention: Drug: daratumumab
  • Experimental: Arm C (Short Intense)
    Intervention: Drug: daratumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 6, 2018)
123
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2014)
120
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date August 6, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of smoldering multiple myeloma (SMM) for less than 5 years
  • Have a confirmed diagnosis of intermediate or high-risk SMM, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

  • Active multiple myeloma,requiring treatment as defined by the study protocol
  • Primary systemic AL (immunoglobulin light chain) amyloidosis
  • Prior or concurrent exposure to any of the following: approved or investigational treatments for SMM or/and multiple myeloma, daratumumab or other anti CD-38 therapies, treatment with corticosteroids with a dose greater than (>) 10 milligram (mg) prednisone per day or equivalent and bone-protecting agents (eg, bisphosphonates, denosumab) or are only allowed if given in a stable dose and for a nonmalignant condition, or received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1
  • History of malignancy (other than SMM) within 3 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
  • Known chronic obstructive pulmonary disease (COPD) OR moderate or severe persistent asthma within the past 2 years
  • Any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Czechia,   France,   Germany,   Israel,   Netherlands,   Russian Federation,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Italy
 
Administrative Information
NCT Number  ICMJE NCT02316106
Other Study ID Numbers  ICMJE CR106449
54767414SMM2001 ( Other Identifier: Janssen Research & Development, LLC )
2014-005139-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP